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Viral load criteria and threshold optimization to improve HIV incidence assay characteristics: A CEPHIA Analysis

Show simple item record Kassanjee, R Pilcher, CD Busch, MP Murphy, G Facente, SN Keating, SM Mckinney, E Marson, K Price, MA Martin, JN Little, SJ Hecht, FM Kallas, EG Welte, A 2018-06-13T14:04:40Z 2018-06-13T14:04:40Z 2016-09-24 2016-09-24
dc.identifier.citation Kassanjee, R, Pilcher, CD, Busch, MP 2016 'Viral load criteria and threshold optimization to improve HIV incidence assay characteristics', AIDS, Vol. 30, No. 15, pp 2361–2371, Viewed online 13 June 2018, Wolters Kluwer , doi: 10.1097/QAD.0000000000001209 en_US
dc.identifier.issn 0269-9370
dc.description.abstract Objective: Assays for classifying HIV infections as ‘recent’ or ‘nonrecent’ for incidence surveillance fail to simultaneously achieve large mean durations of ‘recent’ infection (MDRIs) and low ‘false-recent’ rates (FRRs), particularly in virally suppressed persons. The potential for optimizing recent infection testing algorithms (RITAs), by introducing viral load criteria and tuning thresholds used to dichotomize quantitative measures, is explored. Design: The Consortium for the Evaluation and Performance of HIV Incidence Assays characterized over 2000 possible RITAs constructed from seven assays (Limiting Antigen, BED, Less-sensitive Vitros, Vitros Avidity, BioRad Avidity, Architect Avidity, and Geenius) applied to 2500 diverse specimens. Methods: MDRIs were estimated using regression, and FRRs as observed ‘recent’ proportions, in various specimen sets. Context-specific FRRs were estimated for hypothetical scenarios. FRRs were made directly comparable by constructing RITAs with the same MDRI through the tuning of thresholds. RITA utility was summarized by the precision of incidence estimation. Results: All assays produce high FRRs among treated patients and elite controllers (10–80%). Viral load testing reduces FRRs, but diminishes MDRIs. Context-specific FRRs vary substantially by scenario – BioRad Avidity and Limiting Antigen provided the lowest FRRs and highest incidence precision in scenarios considered. Conclusion: The introduction of a low viral load threshold provides crucial improvements in RITAs. However, it does not eliminate nonzero FRRs, and MDRIs must be consistently estimated. The tuning of thresholds is essential for comparing and optimizing the use of assays. The translation of directly measured FRRs into context-specific FRRs critically affects their magnitudes and our understanding of the utility of assays. en_US
dc.description.sponsorship National Research Foundation (South Africa) en_US
dc.format.extent pagination, illustrations, tables: iii, 18 p. : iII. (some col.). en_US
dc.format.medium PDF en_US
dc.language.iso en en_US
dc.publisher Wolters Kluwer Health, Inc en_US
dc.subject Biomarkers en_US
dc.subject HIV en_US
dc.subject Incidence assays en_US
dc.subject Incidence estimation en_US
dc.subject Optimization en_US
dc.subject Recent infection en_US
dc.subject Viral load en_US
dc.title Viral load criteria and threshold optimization to improve HIV incidence assay characteristics: A CEPHIA Analysis en_US
dc.type Article en_US
dc.rights.holder Wolters Kluwer Health, Inc. en_US

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